Amisulpride Chemical Properties

Melting point:

124-128

Boiling point:

558.9±50.0 °C(Predicted)

Density 

1.200±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: ≥5 mg/mL

form 

solid

pka

13.73±0.46(Predicted)

color 

white

Merck 

14,485

InChI

InChI=1S/C17H27N3O4S/c1-4-20-8-6-7-12(20)11-19-17(21)13-9-16(25(22,23)5-2)14(18)10-15(13)24-3/h9-10,12H,4-8,11,18H2,1-3H3,(H,19,21)

InChIKey

NTJOBXMMWNYJFB-UHFFFAOYSA-N

SMILES

C(NCC1CCCN1CC)(=O)C1=CC(S(CC)(=O)=O)=C(N)C=C1OC

CAS DataBase Reference

71675-85-9(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xn

Risk Statements 

22

Safety Statements 

22-24/25

WGK Germany 

3

RTECS 

CV2308701

HS Code 

2933.99.8290

Toxicity

LD50 in male mice (mg/kg): 56-60 i.v.; 175-180 i.p.; 224-250 s.c.; 1024-1054 orally (Thominet)

MSDS

• Language:English Provider:Amisulpride
• Language:English Provider:SigmaAldrich

Amisulpride Usage And Synthesis

Description

Amisulpride i s a n antipsychotic agent structurally related to sulpiride and sultopride. Useful in the treatment of schizophrenia, it is not, however, without EPS liability.

Chemical Properties

Off-White Solid

Originator

SESIF (Delagrange) (France)

Uses

Neuroleptic agent, an analogue of sulpiride. Used as an antipsychotic. Dopamine receptor antagonist

Uses

Amisulpride is a neuroleptic agent, an analogue of Sulpiride (S689145). Amisulpride is used as an antipsychotic. Amisulpride is a dopamine receptor antagonist.

Definition

ChEBI: Amisulpride is a member of the class of benzamides resulting from the formal condensation of the carboxy group of 4-amino-5-(ethylsulfonyl)-2-methoxybenzoic acid with the primary amino group of 2-(aminomethyl)-1-ethylpyrrolidine. It is a potent, selective dopamine D2 and D3 receptor antagonist. It is an atypical antipsychotic/antischizophrenic agent with limited extrapyrimidal side effects. It has a role as a second generation antipsychotic, a xenobiotic and an environmental contaminant. It is a member of pyrrolidines, an aromatic amine, a sulfone, a member of benzamides and an aromatic amide.

Manufacturing Process

2-Methoxy-4-amino-5-ethylthiobenzoic acid:
159 g of 2-methoxy-4-amino-5-mercaptobenzoic acid, 355 ml of water and 160 ml of caustic soda solution are placed in a flask fitted with a condenser. The mixture is heated until the solid dissolves, then 123 g of ethyl sulfate is added. The mixture is heated to reflux, treated with 10 ml of 30% caustic soda solution, then heated to reflux for 1 hour. After cooling, 800 ml of water is added and the solution is filtered. The precipitate obtained by adding 100 ml of concentrated hydrochloric acid in the presence of ether is drained, washed with water and dried. 162 g of 2-methoxy-4-amino-5-ethylthiobenzoic acid is obtained (yield=88%).
2-Methoxy-4-amino-5-ethylsulfonylbenzoic acid:
123 g of 2-methoxy-4-amino-5-ethylthiobenzoic acid is dissolved hot in 542 ml of acetic acid. The solution obtained is cooled to 35°C, then 185 ml of hydrogen peroxide is added in small quantities while the temperature is raised to 80°C. The temperature is lowered to 40°C and the mixture is kept at that temperature for some hours and then cooled to 10°C. The precipitate formed is drained, washed with acetic acid and dried, then dissolved in 600 ml of water and 100 ml of 20% ammonia. The precipitate formed by adding 70 ml of concentrated hydrochloric acid is cooled, drained, washed with water and dried. 61.5 g of 2-methoxy-4-amino-5-ethylsulfonylbenzoic acid is obtained (yield 42%, M.P. 95-100°C).
4-Amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2- methoxybenzamide:
81 g of 2-methoxy-4-amino-5-ethylsulphonylbenzoic acid and 297 ml of acetone are placed in a flask fitted with an agitator, a thermometer and a dropping funnel, followed by 33 g of triethylamine. The solution is cooled to 0°C, then 30 g of ethyl chloroformate is added drop by drop between 0° and 5°C. When the mixture has been agitated 51 g of 1-ethyl-2- aminomethylpyrrolidine is added drop by drop between 5° and 10°C. The mixture is agitated at 10°C then at ambient temperature. The triethylamine hydrochloride which precipitates is drained, then the acetone is distilled. The residue is dissolved in 600 ml of water in the presence of caustic soda solution. The base crystallizes after seeding and is drained, washed with water and dried. When the crystals have been purified by passing them through hydrochloride and recrystallising them in acetone, 66 g of 4-amino-N-[(1- ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2-methoxybenzamideis obtained (yield 61%, M.P. 126-127°C).

brand name

SOCIAN

Therapeutic Function

Antipsychotic

Biological Activity

Potent, selective dopamine D 2 and D 3 receptor antagonist. K i values are 2.8 and 3.2 nM respectively for human D 2 and D 3 and > 1000 nM for human D 1 , D 4 and D 5 receptors. Shows selectivity for presynaptic dopamine autoreceptors at low doses and blocks postsynaptic D 2 /D 3 receptors at higher doses. Preferentially interacts with limbic D 2 -like receptors in vivo . Atypical antipsychotic/antischizophrenic agent with limited extrapyrimidal side effects and a profile distinct from that of haloperidol and remoxipride.

Biochem/physiol Actions

Amisulpride is a highly selective D2/D3 dopamine receptor antagonist and atypical antipsychotic.

Clinical Use

Treatment of acute and chronic schizophrenia

Drug interactions

Potentially hazardous interactions with other drugs
Alcohol: may enhance CNS effects of alcohol.
Anaesthetics: enhanced hypotensive effect.
Analgesics: increased risk of convulsions with tramadol; enhanced hypotensive and sedative effects with opioids; increased risk of ventricular arrhythmias with methadone - avoid.
Anti-arrhythmics: increased risk of ventricular arrhythmias with anti-arrhythmics that prolong the QT interval; avoid with amiodarone, disopyramide and procainamide (risk of ventricular arrhythmias).
Antibacterials: avoid with erythromycin (increased risk of ventricular arrhythmias).
Antidepressants: increased level of tricyclics.
Antiepileptics: antagonises anticonvulsant effect.
Antihypertensives: increased risk of hypotension.
Antimalarials: avoid with artemether/lumefantrine.
Antipsychotics: increased risk of ventricular arrhythmias with droperidol, sertindole - avoid.
Antivirals: concentration possibly increased by ritonavir.
Anxiolytics and hypnotics: increased sedative effects.
Atomoxetine: increased risk of ventricular arrhythmias.
Beta-blockers: increased risk of ventricular arrhythmias with sotalol.
Cytotoxics: increased risk of ventricular arrhythmias with vandetanib - avoid; increased risk of ventricular arrhythmias with arsenic trioxide.
Diuretics: increased risk of ventricular arrhythmias due to hypokalaemia.
Pentamidine: increased risk of ventricular arrhythmias - avoid.

Metabolism

Amisulpride is weakly metabolised: two inactive metabolites, accounting for approximately 4% of the dose, have been identified. Amisulpride is eliminated unchanged in the urine. Fifty percent of an intravenous dose is excreted via the urine, of which 90% is eliminated in the first 24 hours.

storage

-20°C

References

[1] schoemaker h1, claustre y, fage d, rouquier l, chergui k, curet o, oblin a, gonon f, carter c, benavides j, scatton b. neurochemical characteristics of amisulpride, an atypical dopamine d2/d3 receptor antagonist with both presynaptic and limbic selectivity. j pharmacol exp ther. 1997 jan;280(1):83-97.

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